Presented at the annual ECTRIMS conference (London, September 14-17, 2016):
Rituximab in multiple sclerosis; data from the Swedish MS registry
P. Alping1, A. Svenningsson2, J. Salzer3, J. Burman4, C. Dahle5, K. Fink1, J. Hillert1, J. Lycke6, A.-M. Landtblom4, C. Martin2, P. Nilsson7, F. Walentin8, T. Olsson1, T. Frisell9, F. Piehl1
1Clinical neuroscience, 2Clinical Science Danderyd´s Hospital, Karolinska Institutet, Stockholm, 3Pharmacology and Clinical Neuroscience, Umeå University, Umeå, 4Neuroscience, Uppsala University, Uppsala, 5Clinical and Experimental Medicine, Linköping University, Linköpin, 6Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, 7Neurology, Lund University, Lund, 8Neurology, Örebro University Hospital, Örebro, 9Medicine Solna, Karolinska Institutet, Stockholm, Sweden
Background:
Rituximab (RTX) is a monoclonal anti-CD20 B-cell depleting antibody. Two smaller randomized studies in MS have shown promising effects of RTX, both in relapsing-remitting MS (RRMS) and in primary progressive MS (PPMS).
Furthermore, in an observational study we recently found that disease reactivation after terminating natalizumab due to positive JC-virus serology was much lower for RTX compared with fingolimod (Alping et al., Ann Neurol2016 PMID: 27038238). In Sweden the off-label use of RTX for MS, especially in JCV+ RRMS and inflammatory active progressive MS, has increased rapidly over the last years.
Objective:
To describe and compare baseline characteristics and outcomes for patients starting RTX, FGL, or NTZ therapy, for MS, in Sweden, using data from the Swedish MS register (SMSreg).
Methods:
Baseline and follow up data on all patients treated with RTX, FGL, and NTZ were retrieved from the SMSreg.
Results:
In our preliminary data set, we identified 2041 MS patients treated with RTX (until 1 Dec 2015). These patients correspond to 25.3% of all patients with disease modulatory treatment, or 14.9% of all active MS patients in SMSreg. The mean age was 43.6 years, 68.9% were female, and the listed disease course was 68.4% RRMS, 23.6% secondary progressive MS (SPMS) and 6.1% PPMS. The mean disease duration was 11.3 years and the mean treatment duration 21.1 months.
At start of therapy the mean expanded disability status scale (EDSS) was 3.22, symbol digit modalities test (SDMT) 50.8, multiple sclerosis impact scale-29 (MSIS) 1.94 (physical) and 2.30 (psychological), respectively. The proportion of patients who terminated RTX therapy for all reasons was 9.3%.
Additional data on effects over time on EDSS, SDMT and MSIS-29 will be included in the final presentation, as well as corresponding data for the FGL and NTZ cohorts.
Conclusions:
We here report the largest cohort of MS patients treated with RTX over an extended period of time. Preliminary results indicate that RTX demonstrates a high degree of drug survival, with few treatment interruptions due to an inadequate treatment response or adverse events. Furthermore, we will also present a comparison between RTX, FGL, and NTZ, thus shedding further light on the role RTX in the treatment of MS.
______________
Disclosure:
Peter Alping and Thomas Frisell; nothing to disclose.
Anders Svenningsson has received travel support and/or lecture honoraria from Biogen, Merck Serono, Genzyme, Novartis and Baxter, and has received unconditional research grants from Bayer Schering Pharma and Biogen.
Jonatan Salzer has received lecture honoraria from Biogen, Teva and Genzyme and has received travel support from Biogen and research support from Synapsys.
Joachim Burman has received travel support and/or lecture honoraria from Almirall, Biogen, Genzyme, Hospira and MerckSerono, and has received unconditional research grants from Biogen and MerckSerono.
Charlotte Dahle has received unrestricted research grants or honoraria for lectures or advisory boards from Biogen, Novartis, Merck Serono, Teva and Genzyme.
Katharina Fink has received an unrestricted academic research grant from Biogen and compensation for lectures from Biogen and Novartis, which have been exclusively used to support research activities.
Jan Hillert has received honoraria for serving on advisory boards for Biogen and Novartis, speaker's fees from Biogen, MerckSerono, Bayer-Schering, Teva and Sanofi-Aventis and received unrestricted research support from, Biogen, MerckSerono, Genzyme and Novartis.
Anne-Marie Landtblom has received honoraria from MerckSerono, Teva, Biogen and Genzyme.
Jan Lycke has received travel support and/or lecture honoraria from Bayer Schering Pharma, Biogen, Novartis, Teva and Genzyme , has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme, has received unconditional research grants from Biogen, Novartis and Teva, and serves on the editorial board of the Acta Neurologica Scandinavica.
Claes Martin has received honoraria for lectures and advisory boards from Biogen, Novartis, Merck Serono, Teva and Genzyme.
Petra Nilsson has received travel support from Bayer Schering Pharma, MerckSerono, Biogen and Genzyme, honoraria for lectures and advisory boards from MerckSerono and Genzyme, compensation for participation in advisory boards for Novartis and Roche, lectures for Biogen and has received unrestricted grants from Biogen.
Fredrik Walentin has received research grants from Biogen and MerckSerono.
Tomas Olsson has received compensation for lectures and /or advisory boards, or unrestricted MS research grants from Biogen, Allmiral, Novartis, Genzyme, Astrazeneca and MerckSerono.
Fredrik Piehl has received unrestricted academic research grants from Biogen, Genzyme and Novartis, and travel support and/or compensation for lectures and/or participation in advisory boards from Biogen, Merckserono, Novartis, Genzyme and Teva, which have been exclusively used for the support of research activities.
Rituximab in multiple sclerosis; data from the Swedish MS registry
P. Alping1, A. Svenningsson2, J. Salzer3, J. Burman4, C. Dahle5, K. Fink1, J. Hillert1, J. Lycke6, A.-M. Landtblom4, C. Martin2, P. Nilsson7, F. Walentin8, T. Olsson1, T. Frisell9, F. Piehl1
1Clinical neuroscience, 2Clinical Science Danderyd´s Hospital, Karolinska Institutet, Stockholm, 3Pharmacology and Clinical Neuroscience, Umeå University, Umeå, 4Neuroscience, Uppsala University, Uppsala, 5Clinical and Experimental Medicine, Linköping University, Linköpin, 6Clinical Neuroscience and Rehabilitation, University of Gothenburg, Gothenburg, 7Neurology, Lund University, Lund, 8Neurology, Örebro University Hospital, Örebro, 9Medicine Solna, Karolinska Institutet, Stockholm, Sweden
Background:
Rituximab (RTX) is a monoclonal anti-CD20 B-cell depleting antibody. Two smaller randomized studies in MS have shown promising effects of RTX, both in relapsing-remitting MS (RRMS) and in primary progressive MS (PPMS).
Furthermore, in an observational study we recently found that disease reactivation after terminating natalizumab due to positive JC-virus serology was much lower for RTX compared with fingolimod (Alping et al., Ann Neurol2016 PMID: 27038238). In Sweden the off-label use of RTX for MS, especially in JCV+ RRMS and inflammatory active progressive MS, has increased rapidly over the last years.
Objective:
To describe and compare baseline characteristics and outcomes for patients starting RTX, FGL, or NTZ therapy, for MS, in Sweden, using data from the Swedish MS register (SMSreg).
Methods:
Baseline and follow up data on all patients treated with RTX, FGL, and NTZ were retrieved from the SMSreg.
Results:
In our preliminary data set, we identified 2041 MS patients treated with RTX (until 1 Dec 2015). These patients correspond to 25.3% of all patients with disease modulatory treatment, or 14.9% of all active MS patients in SMSreg. The mean age was 43.6 years, 68.9% were female, and the listed disease course was 68.4% RRMS, 23.6% secondary progressive MS (SPMS) and 6.1% PPMS. The mean disease duration was 11.3 years and the mean treatment duration 21.1 months.
At start of therapy the mean expanded disability status scale (EDSS) was 3.22, symbol digit modalities test (SDMT) 50.8, multiple sclerosis impact scale-29 (MSIS) 1.94 (physical) and 2.30 (psychological), respectively. The proportion of patients who terminated RTX therapy for all reasons was 9.3%.
Additional data on effects over time on EDSS, SDMT and MSIS-29 will be included in the final presentation, as well as corresponding data for the FGL and NTZ cohorts.
Conclusions:
We here report the largest cohort of MS patients treated with RTX over an extended period of time. Preliminary results indicate that RTX demonstrates a high degree of drug survival, with few treatment interruptions due to an inadequate treatment response or adverse events. Furthermore, we will also present a comparison between RTX, FGL, and NTZ, thus shedding further light on the role RTX in the treatment of MS.
______________
Disclosure:
Peter Alping and Thomas Frisell; nothing to disclose.
Anders Svenningsson has received travel support and/or lecture honoraria from Biogen, Merck Serono, Genzyme, Novartis and Baxter, and has received unconditional research grants from Bayer Schering Pharma and Biogen.
Jonatan Salzer has received lecture honoraria from Biogen, Teva and Genzyme and has received travel support from Biogen and research support from Synapsys.
Joachim Burman has received travel support and/or lecture honoraria from Almirall, Biogen, Genzyme, Hospira and MerckSerono, and has received unconditional research grants from Biogen and MerckSerono.
Charlotte Dahle has received unrestricted research grants or honoraria for lectures or advisory boards from Biogen, Novartis, Merck Serono, Teva and Genzyme.
Katharina Fink has received an unrestricted academic research grant from Biogen and compensation for lectures from Biogen and Novartis, which have been exclusively used to support research activities.
Jan Hillert has received honoraria for serving on advisory boards for Biogen and Novartis, speaker's fees from Biogen, MerckSerono, Bayer-Schering, Teva and Sanofi-Aventis and received unrestricted research support from, Biogen, MerckSerono, Genzyme and Novartis.
Anne-Marie Landtblom has received honoraria from MerckSerono, Teva, Biogen and Genzyme.
Jan Lycke has received travel support and/or lecture honoraria from Bayer Schering Pharma, Biogen, Novartis, Teva and Genzyme , has served on scientific advisory boards for Almirall, Teva, Biogen, Novartis and Genzyme, has received unconditional research grants from Biogen, Novartis and Teva, and serves on the editorial board of the Acta Neurologica Scandinavica.
Claes Martin has received honoraria for lectures and advisory boards from Biogen, Novartis, Merck Serono, Teva and Genzyme.
Petra Nilsson has received travel support from Bayer Schering Pharma, MerckSerono, Biogen and Genzyme, honoraria for lectures and advisory boards from MerckSerono and Genzyme, compensation for participation in advisory boards for Novartis and Roche, lectures for Biogen and has received unrestricted grants from Biogen.
Fredrik Walentin has received research grants from Biogen and MerckSerono.
Tomas Olsson has received compensation for lectures and /or advisory boards, or unrestricted MS research grants from Biogen, Allmiral, Novartis, Genzyme, Astrazeneca and MerckSerono.
Fredrik Piehl has received unrestricted academic research grants from Biogen, Genzyme and Novartis, and travel support and/or compensation for lectures and/or participation in advisory boards from Biogen, Merckserono, Novartis, Genzyme and Teva, which have been exclusively used for the support of research activities.
Comment